The overall goal of this ICMIC is to develop and use advanced imaging approaches to gain in-depth knowledge of critical cancer targets, pathways and cellular function. This information will ultimately be used to identify new therapeutic points of attack and to guide clinical trials with prominent drug development candidates. To this end, we have brought together a multi-disciplinary team of basic and clinical investigators who will function as a single intellectual unit in the development of imaging approaches for targeted therapeutic applications. Project 1 (Weissleder) will focus on the development of effective new imaging agents for intracellular cancer targets using a novel bioorthogonal chemistry. Project 2 (Mazitschek, Clardy) will develop and test imaging approaches for different histone deacetylase (HDAC), enzymes associated with epigenetic gene regulation and which are strongly implicated in cancer. Project 3 (Lin, Scadden) will harness vanguard technologies to image and better understand the clonal fates of tumor cells and their associated stromal cells. Project 4 (Pittet) will investigate tumor-associated immune responses, and the effects of therapies on these responses. There will be two Developmental Fund Projects per year, the aims of which will be to attract new investigators to the P50, stimulate creative high-impact research, rapidly test new ideas, and fund promising collaborative work. The highly effective Career Development Program will continue to provide new junior investigators with the necessary multidisciplinary skills for a successful research career in cancer imaging. The above projects and programs will be facilitated by state-of-the art, highly innovative Specialized Resources in Chemistry (Hilderbrand), and in Mouse Imaging and Analysis (Nahrendorf). Fiscal management and oversight, as well as IT and statistical support will be provided by an Administration, Statistics and IT Core (Weissleder). Together, these ICMIC components will work synergistically to a) incorporate molecular imaging into pioneering cancer research at Harvard/MGH, and b) encourage the translation of molecular imaging to the practice of cancer diagnosis, management and therapy.